Vudalimab for Advanced Gynecologic and Genitourinary Cancers

Not currently recruiting at 18 trial locations

Overseen By Jolene Shorr

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Xencor, Inc.

Must be taking: LHRH analogues

Must not be taking: CTLA4 agents, PD1 therapies

Disqualifiers: Autoimmune disease, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called vudalimab for individuals with advanced gynecologic (female reproductive system) and genitourinary (urinary and male reproductive systems) cancers. The goal is to determine if vudalimab can safely and effectively treat these cancers, especially when other treatments have failed. It suits those whose cancer has returned or continued to grow despite standard treatments like chemotherapy. Participants must have specific types of cancer, such as ovarian, cervical, or prostate cancer, and should be willing to follow the study schedule. As a Phase 2 trial, this research measures how well vudalimab works in an initial, smaller group of people, offering early access to a potentially effective treatment.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot be on other anticancer therapies, except for certain hormone therapies for prostate cancer. If you're on systemic corticosteroids or immunosuppressive medications, you must stop them 14 days before starting the trial drug.

Is there any evidence suggesting that vudalimab is likely to be safe for humans?

Research has shown that vudalimab (also known as XmAb20717) is under investigation for its safety in individuals with advanced gynecologic and genitourinary cancers. While specific safety details from these studies are not provided, it is important to note that this treatment is in Phase 2 trials. This phase indicates that it demonstrated some safety in early trials and is now being tested in larger groups to further assess its effects and potential side effects.

Vudalimab is a bispecific antibody, designed to target cancer cells more precisely, potentially reducing unwanted side effects. However, like any new treatment, risks exist, and side effects may vary.

Prospective trial participants should remember that researchers closely monitor safety and prioritize participants' well-being. Discuss any concerns with the study team to understand what to expect. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vudalimab is unique because it targets both PD-1 and CTLA-4 pathways, which are crucial checkpoints in the immune system that help cancer cells evade detection. Unlike standard treatments for advanced gynecologic and genitourinary cancers, which often rely on chemotherapy or single checkpoint inhibitors, Vudalimab combines dual checkpoint inhibition in one therapy. This dual action could potentially enhance the immune system's ability to fight cancer more effectively, offering a new hope for patients with advanced stages of these cancers. Researchers are excited because this approach may lead to better outcomes with possibly fewer side effects compared to traditional treatments.

What evidence suggests that vudalimab might be an effective treatment for advanced gynecologic and genitourinary cancers?

Research shows that vudalimab, also known as XmAb20717, is designed to help the immune system fight certain advanced gynecologic and genitourinary cancers. In early studies, vudalimab showed promise by targeting two proteins, PD-1 and CTLA-4, which normally prevent the immune system from attacking cancer cells. These proteins can act like shields for cancer, and vudalimab works to remove them. Initial findings suggested that patients with advanced solid tumors experienced some positive outcomes when treated with vudalimab. While more research is needed to fully understand its effectiveness, the early results are encouraging for those with these hard-to-treat cancers. ^{2 3 4 5 6}

Who Is on the Research Team?

Jolene Shorr

Principal Investigator

Xencor, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with certain advanced gynecologic and genitourinary cancers that have worsened despite all approved treatments or when no suitable treatments are available. Participants must be in good physical condition, agree to use effective birth control, and commit to the study schedule. Those who've had more than two chemo treatments for some cancers or recent other cancer therapies can't join.

Inclusion Criteria

Able to provide written informed consent

I am willing and able to follow the study's schedule completely.

My cancer type has been confirmed through lab tests.

Exclusion Criteria

Subject is pregnant or breastfeeding or planning to become pregnant while enrolled in the study

I have previously been treated with specific immunotherapy.

I do not have HIV, hepatitis C, or hepatitis B.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Stage 1 Treatment

Participants receive vudalimab in tumor-specific cohorts to evaluate efficacy and safety

12 weeks

Stage 2 Treatment

Additional subjects are enrolled in cohorts with ORR ≥ 20% for further evaluation

Variable, based on cohort expansion

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Vudalimab (XmAb20717)

Trial Overview The trial is testing Vudalimab (XmAb20717) on patients with specific advanced cancers of the reproductive organs and urinary system. It's an open-label Phase 2 study, meaning both researchers and participants know what treatment is being given, aiming to assess how well it works and its safety.

How Is the Trial Designed?

Group I: vudalimab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Xencor, Inc.

Lead Sponsor

Trials

31

Recruited

2,500+

ICON plc

Industry Sponsor

Trials

88

Recruited

28,900+

Dr. Steve Cutler

ICON plc

Chief Executive Officer since 2017

PhD from the University of Sydney, MBA from the University of Birmingham

Dr. Greg Licholai

ICON plc

Chief Medical Officer since 2023

Degrees from Harvard Business School, Yale School of Medicine, Columbia University, and Boston College

Published Research Related to This Trial

Avelumab demonstrated antitumor activity in patients with platinum-refractory metastatic urothelial carcinoma, achieving a complete or partial response in 17% of treated patients, including 6% with complete responses.

The safety profile of avelumab was manageable, with most treatment-related adverse events being mild (grade 1-2), although there were serious adverse events in 8% of patients, including one treatment-related death from pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Patel, MR., Ellerton, J., Infante, JR., et al.[2022]

In a study of 204 patients with advanced urothelial carcinoma, those receiving maintenance avelumab therapy showed longer overall survival compared to those receiving second-line pembrolizumab or cytotoxic chemotherapy, although progression-free survival was not significantly different.

Patients who started maintenance avelumab therapy within 6 weeks of completing first-line chemotherapy had a higher disease control rate (77%) compared to those who waited longer, suggesting that early initiation of avelumab may enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study. Miyake, M., Shimizu, T., Oda, Y., et al.[2023]

The combination of anti-PD-1 and anti-CTLA4 antibodies has improved cancer treatment outcomes but is often limited by serious immune-related side effects and resistance.

MEDI5752, a new bispecific antibody targeting both PD-1 and CTLA4, aims to enhance treatment effectiveness by focusing on T cells that have already encountered antigens, potentially increasing efficacy while reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies to PD-1 and CTLA4: Doubling Down on T Cells to Decouple Efficacy from Toxicity. Burton, EM., Tawbi, HA.[2021]

Checkpoint-blocking antibodies, like ipilimumab, enhance the immune system's ability to recognize and eliminate tumors by blocking the CTLA-4 receptor, which normally inhibits T-cell activation.

The review discusses the clinical development of CTLA-4 blocking antibodies, highlighting their effectiveness in cancer treatment, associated toxicities, and the exploration of biomarkers to predict patient responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity, Toxicity, Biomarkers, and Future Development of CTLA-4 Checkpoint Antagonists. Callahan, MK., Wolchok, JD.[2017]

Immunologic checkpoint blockade using antibodies like ipilimumab (CTLA-4) and pembrolizumab (PD-1) has shown effectiveness in treating advanced melanoma and is expected to gain further approvals for other cancers.

These treatments can lead to unique immune-related adverse events and unusual tumor response patterns, prompting research into combination therapies to potentially enhance their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Checkpoint Blockade in Cancer Therapy. Postow, MA., Callahan, MK., Wolchok, JD.[2022]

Zimberelimab (GLS-010) is a highly effective human monoclonal antibody that binds strongly to the PD-1 receptor, blocking its interaction with PD-L1/2, which is crucial for T cell activation.

In preclinical studies, GLS-010 demonstrated significant anti-tumor effects in mice, indicating its potential as a promising treatment for cancer, warranting further investigation in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Characterization of GLS-010 (Zimberelimab), a Novel Fully Human Anti-PD-1 Therapeutic Monoclonal Antibody for Cancer. Lou, B., Wei, H., Yang, F., et al.[2022]

In the JAVELIN Lung 100 trial involving 1214 patients with advanced NSCLC, avelumab showed longer median progression-free survival (PFS) compared to platinum-based chemotherapy (8.4 months vs. 5.6 months), indicating its potential efficacy as a first-line treatment.

Although avelumab demonstrated longer median overall survival (OS) compared to chemotherapy (20.1 months vs. 14.9 months), the differences were not statistically significant, suggesting that while avelumab may be beneficial, it did not meet the primary objective of the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1-Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial. Reck, M., Barlesi, F., Yang, JC., et al.[2023]

Recent advancements in treating genitourinary tumors, particularly renal cell and prostate cancer, involve using immune checkpoint inhibitors like ipilimumab and nivolumab to enhance the immune response against cancer cells.

Initial data shows promising results for these immunomodulating antibodies, highlighting the need for further investigation in large controlled trials to fully understand their therapeutic potential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunologic checkpoints blockade in renal cell, prostate, and urothelial malignancies. Bracarda, S., Altavilla, A., Hamzaj, A., et al.[2015]

The bispecific antibody described in patent US2019161548 targets both PD-1 and CTLA-4, which are important immune checkpoints in cancer, and has been shown to enhance the activation and proliferation of CD8+ T cells and stimulate CD4+ T cells.

Clinical trials are currently underway to assess the safety and effectiveness of this bispecific antibody, with hopes that it may outperform the existing combination therapy of nivolumab and ipilimumab in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific anti-PD-1/CTLA-4 antibody for advanced solid tumors. Perez-Santos, M.[2021]

In a preoperative trial involving 12 patients with localized bladder cancer, the anti-CTLA-4 antibody ipilimumab demonstrated a tolerable safety profile, with most adverse events being mild (grade 1/2).

The treatment led to measurable immune responses, specifically an increase in CD4+ICOShi T cells, which correlated with improved overall survival in a retrospective analysis of metastatic melanoma patients, suggesting that these T cells could serve as a marker for clinical benefit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Carthon, BC., Wolchok, JD., Yuan, J., et al.[2023]

The JAVELIN Ovarian 200 trial is the first Phase III study to investigate the effectiveness of avelumab, a PD-L1 checkpoint inhibitor, in treating women with platinum-resistant ovarian cancer, involving multiple treatment arms to assess its efficacy.

The trial will measure overall survival and progression-free survival as primary outcomes, providing valuable insights into the potential benefits of avelumab alone or in combination with doxorubicin compared to doxorubicin alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avelumab (anti-PD-L1) in platinum-resistant/refractory ovarian cancer: JAVELIN Ovarian 200 Phase III study design. Pujade-Lauraine, E., Fujiwara, K., Dychter, SS., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS5097

A phase 2, multicenter, parallel-group, open-label study of ... This Phase 2 study is designed to evaluate the safety and antitumor activity of vudalimab in combination with other anticancer agents or alone in subgroups of ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05032040

XmAb20717 (Vudalimab)in Patients With Selected ... This is a Phase 2, multicenter, two-stage, open-label, parallel-group study designed to evaluate the efficacy and safety of vudalimab (XmAb20717)

3. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5296

A Study of XmAb20717 (Vudalimab)in Patients With ... A Study of XmAb20717 (Vudalimab)in Patients With Selected Advanced Gynecologic and Genitourinary Malignancies ; Status. Active ; Cancer Type. Cervical Cancer.

4. withpower.com withpower.com/trial/phase-3-adenomyoepithelioma-11-2021-e8861

Vudalimab for Advanced Gynecologic and Genitourinary ... This trial is testing a new drug called vudalimab in patients with hard-to-treat advanced gynecologic and genitourinary cancers. The drug aims to boost the ...

5. investors.xencor.com investors.xencor.com/news-releases/news-release-details/xencor-presents-updated-data-phase-1-study-vudalimab-pd-1-x-ctla

Xencor Presents Updated Data from the Phase 1 Study of ... Data from its Phase 1 study evaluating vudalimab (XmAb 717), a PD-1 x CTLA-4 bispecific antibody, in patients with advanced solid tumors (DUET-2).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05032040?cond=%22Clear%20Cell%20Adenocarcinoma%22&intr=%22antibodies%22&viewType=Table&rank=5

A Study of XmAb20717 (Vudalimab)in Patients With ... Types of outcome measures include primary outcome measure and secondary outcome measure. ... A type of intervention model describing a clinical trial in which two ...